• Toxicological Research
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• 제21권2호
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• pp.115-119
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• 2005

In the present study, we evaluated the free radical scavenging and xanthine oxidase inhibitory activities exhibited by extracts obtained from the dried stems (and leaves) of Lespedeza bicolor We also assessed its potential irritation activities with regard to cosmetic use. When the DPPH radical scavenging activities of L. bicolor were assessed at six different concentrations (0, 50, 100, 250, 500 and 1000 ${\mu}g/ml$), the concentration of L. bicolor required to inhibit DPPH radical formation by $50\%$ was found to be $164.90{\mu}g/ml$. The effects of L. bicolor on the inhibition of xanthine oxidase were determined at seven different concentrations. The $50\%$ effective concentration was found to be $282.75{\mu}g/ml$. In the skin irritation test, all animals survived for the duration of the study, and all exhibited normal gains in body weight. The control sites exhibited no response to the control procedures. No edema, erythema, or eschar formation was observed in any of the tested rabbits. In the ocular irritation study, all of the rabbit eyes remained normal. In summary, L. bicolor extracts were considered to be non-irritating to the skin and eye.

• Toxicological Research
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• 제33권3호
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• pp.191-203
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• 2017

Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornealike epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.173-178
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• 2000

The purpose of this work is to develop a transurethral suppository containing prostaglandin $E_1\;(PGE_1)$, which stabilizes the drug, gives no irritation to physiological body and enhances the erectile response of $PGE_1.\;PGE_1$ transurethral suppositories were prepared with various amounts of compositions such as saturated polyglycolysed glyceride $(Suppocire^{\circledR}\;AP,\;SAP)$, polyoxyethylene hydrogenated castor oil (HCO-50) and ethanol. The melting points, viscosities and $PGE_1$ release of the suppositories were investigated. Ocular irritation test was carried out after application of $PGE_1$ suppository to rabbit's eye. The intracavernous pressure (ICP), penile length and duration of erectile response were determined after transurethral administration of $PGE_1$ suppository and compared with those after intracavernosal injection of $PGE_1$ solution to cats. HCO-50 hardly affected the melting points and viscosities of $PGE_1$ suppositories. Additionally, $PGE_1$ transurethral suppositories, whose melting point ranges was $34-35^{\circ}C$, was speedily melted in physiological body. HCO-50 significantly decreased the dissolution rates of $PGE_1$ from the suppositories. Dissolution mechanism analysis showed the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppositories by Fickian diffusion. The release rate of $PGE_1$ from $PGE_1$ suppository [PGE1/SAP/HCO-50/ethanol (1/94.5/2.5/2%)] was about 80% within 2 h. This $PGE_1$ suppository gave no significant irritation to the ocular tissue, expecting that it gave no irritation to the urethral tissue less sensive than ocular tissue. Furthermore, $PGE_1$ in this suppository was stable at $4^{\circ}C$ for 2 years. This suppository increased the ICP and penile erection similar to those of injectable $PGE_1$ solution. However, it gave 2.5-fold increased duration of erectile response than injectable $PGE_1$ solution. Our results suggested that it gave more effective erectile response than injectable $PGE_1$ solution in cats. It is concluded that this $PGE_1$ suppository with good safety, excellent stability and enhanced erectile response, could be a more effective and convenient transurethal delivery system of $PGE_1$.

• 한국안광학회지
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• 제10권4호
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• pp.293-304
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• 2005

렌즈 세척제인 ReNu$^{TM}$의 안자극테스트를 한국식품의약품안전청의 고시에 따라서 Draize방법(1959)을 사용하여 분석하였다. 부가해서 검사 항목의 잠재성 독성테스트를 위해서 염증세포와 비염증세포의 비율에서 역시 눈 분비물에 대한 세포도말표본사용으로 관찰하였다. 검사에서 각막, 홍채, 망막, 그리고 공막에 대한 조직학적 변화들은 역시 모든 실험동물에서 관찰되었다. 각막과 결막의 약간 자극성은 벼비척그룹에서 점안후 1, 2, 3일에서 관찰되었다. 이러한 지점에서의 안점막자극지수(MIOI)는 각각 4.17, 3.00, 1.33으로 확인되었다. 세척군에서 각막과 결막의 약간의 자극은 각각 0.67과 1.33으로서 MIOI로서 점안후 1일과 2일에서 관찰되었다. 따라서 ReNu$^{TM}$은 비자극성 물질로 생각된다. 왜냐하면 MIOI는 세척군과 비세척군 모두에서 전체 실험기간을 통해서 5.00이하로 관찰되었다. 급성안자극계수(IAOI)는 역시 4.17로서 확인되었다(점안후 일일). 일부의 예외들은 비세척군의 점안후 1일에서 분비물에서 염증세포 비율의 경향이 증가되었다. 그러나 유의성은 없었다. 한편 안분비물의 도말세포관찰에서 의미있는 변화들은 본 연구에서 관찰되었다. 부가해서 각막, 홍채, 공막 위에서 비정상조직 변화는 역시 비처리된 대군군 눈과 비교해서 ReNu$^{TM}$, 점안군에서는 탐지되지 않았다.

• Toxicological Research
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• 제26권1호
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• pp.9-14
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• 2010

The evaluation of eye and skin irritation potential is essential to ensuring the safety of human in contact with a wide variety of substances. Despite this importance of irritation test, little is known with respect to the irritation potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate the tendency of lomefloxacin to cause eye and skin irritation, we carried out in vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test using $KeraSkin^{TM}$ human skin model system. 3T3 neutral red uptake assay has been proposed as a potential replacement alternative for the Draize Eye irritation test. In this study, the $IC_{50}$ value obtained for lomefloxacin was 375 ${\mu}g$. According to the classification model used for determining in vitro categories, lomefloxacin was classified as moderately irritant. For evaluation of skin irritation, engineered epidermal equivalents ($KeraSkin^{TM}$) were subjected to 10 and 25 mg of lomefloxacin for 15 minutes. Tissue damage was assessed by tissue viability evaluation, and by the release of a pro-inflammatory mediator, interleukin- 1${\alpha}$. Lomefloxacin increased the interleukin-1${\alpha}$ release after 15 minutes of exposure and 42 hours of post incubation, although no decrease in viability was observed. Therefore, lomefloxacin is considered to be moderately irritant to skin and eye.

• Biomolecules & Therapeutics
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• 제2권3호
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• pp.247-255
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• 1994

As a series of safety studies of DA-3030, a new rhO-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(single), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5mι of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days.4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.195-195
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• 2002

In recent years, the safety of sunscreens has been challenged based on the reports of its adverse effect on users; dermatitis, allergic contact dermatitis, photoallergic contact dermatitis. To investigate a correlation between sun protection factor (SPF) and the safety of sunscreens, we measured in vitro SPF index using homosalate as a standard and examined the toxicity tests on cosmetics; primary skin irritation tests, ocular irritation test, and skin sensitization test.(omitted)

• 한국안광학회지
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• 제11권4호
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• pp.299-310
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• 2006

시판중인 렌즈 보존액 중 가장 흔히 사용 또는 유통되고 있는 $SOLOCARE^{TM}$에 대한 안점막자극성시험을 식품의약품 안전청 고시에 따라 Draize법을 이용하여 그 자극성의 정도를 평가하고, 눈에 가해질 수 있는 잠재적인 독성을 평가하기 위하여, 배출물에 대한 도말표본 상에서 염증세포 및 비 염증성 유상피세포가 차지하는 비율과 함께 점안 후 안구 중, 각막, 홍채, 망막 및 공막의 조직병리학적 관찰을 실시한 결과 다음과 같은 결과를 얻었다. 비 세척군에서는 점안 후1, 2 및 3일에 국한하여, 각막과 결막에 경미한 자극이 관찰되어, 이 기간 동안의 평균 안점막 자극지수(Mean Index of Ocular Irritation; MIOI)가 각각 4.33, 3.33 및 2.00으로 관찰되었으며, 세척군에서는 점안 후 1 및 2일에 국한하여, 결막에서 경미한 자극성이 인정되었고, 이때 MIOI는 각각 3.00과1.33으로 관찰되었다. 따라서 $SOLOCARE^{TM}$는 세척군 및 비세척군 모두에서 MIOI가 모든 관찰기간에서 5.00 이하로 관찰되었으며, 관찰기간 중 MIOI의 최대값인 IAOI(The Index of Acute Ocular Irritation) 역시점안 1일후 4.33로 관찰되어 무자극성 물질로 관찰되었다. 한편 배출물에 대한 염증성 세포의 비율은 무처치 대조군과 비교하여 점안초기 유의성은 인정되지 않았으나, 다소 증가된 경향을 나타낸 이외 의미있는 변화는 인정되지 않았다. 또한 안구의 조직병리학적 검사에서 각막, 홍채, 망막 및 공막 모두에서 무처치 대조군과 비교하여 의미 있는 변화는 인정되지 않았다.

• Toxicological Research
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• 제18권1호
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• pp.79-85
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• 2002

YHB216 is one of new recombinant human erythropoietins (rHu-EPO) developed by Yuhan Research Institute. The rHu-EPO products are widely being used for the treatment of various types of anemia. As a series of safety studies on YHB216, we performed the local irritation test (dermal & ocular application) in male New Zealand White rabbits and micronucleus test in male ICR mice. In the skin irritation test, 0.5 ml of YHB216 10,000 IU/ml solution was applied to the back skin of rabbits for 24 hours and sub-sequent observation was performed. There was no induced response after the treatment and the primary irritation index (P.I.I.) was‘0’. In the eye irritation test, 0.1 ml of YHB216 10,000 IU/mL solution was instilled into the conjunctiva of the eye. No treatment-related reaction was observed at the cornea, iris, and conjunctiva. In the micronucleus test, YHB216 was administered intravenously to male mice (6 mice per group) at dose levels of 0, 6,250, 12,500, and 25,000 IU/kg. Bone marrow cells were collected at 24 hours after the treatment. YHB216 treated groups showed no significant difference in the P/N (polychromatic erythrocyte/ normochromatic erythrocyte) ratio and in the number of micronucleated polychromatic erythrocyte com-pared with the control. In conclusion, YHB216 was found to be a non-irritating material up to 10,000 IU/ml in the local irritation test and to be a non-mutagen up to 25,000 IU/kg in the micronucleus test.

• Toxicological Research
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• 제14권3호
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• pp.393-400
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• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.